The incorporation of fluorine into fine chemicals has had a significant impact in the chemical, agrochemical, and pharmaceutical industries. For example, difluoromethyl groups may serve as bioisosteric replacements and surrogates for oxygen in compounds, providing greater stability (Blackburn, et al. J. Chem. Soc. Chem. Commun. 1981, 930) and as useful blocking groups (Fukuda, et al. Tetrahedron 1996, 52, 157). Drug candidates that contain trifluoromethyl groups, compared to non-fluorinated counterparts, often display better biological activities, including increased lipophilicity, bioavailability, binding affinity, metabolic stability, and membrane permeability (Ojima, et al. Medicinal Chemistry and Chemical Biology, John Wiley & Sons).
Preparations of varieties of chemical compounds that contain fluoro groups are challenging. For example, Olah and Prakash discovered a synthon for adding difluorinated methyl groups (Prakash, et al. Angew. Chem. Int. Ed. 2003, 42, 5216). A synthon-based approach, however, limits the scope of the starting materials and efficiency of a synthetic plan. Methods of the introduction of trifluoromethyl groups involve expensive or toxic reagents (Ichikawa, et al. Chem. Lett. 1981, 12, 1679-1680; (Boechat, et al. Current org. Syn. 2010, 403-413) or gaseous fluoroform (Folleas, et al. Tetrahedron, 2000, 56, 275-283). There is an ongoing need for synthetic methods for preparation of fluoro groups-containing compounds that can be compatible with a large scope of substrates and under mild reaction conditions.